Makindo Medical Notes

Related Subjects: |X linked Agammaglobulinaemia (Bruton) |X-linked lymphoproliferative disease (Children) |Chediak Higashi syndrome |Common variable immunodeficiency |Severe combined immunodeficiency disorders |DiGeorge syndrome (thymic aplasia) |Selective IgA deficiency |Wiskott-Aldrich syndrome (Children) |T lymphocytes

Problems begin after 6 months of life when maternal immunoglobulins (Ig) levels drop.

About

• X-linked Agammaglobulinaemia (XLA), also known as Bruton's disease, was first described by Dr. Bruton in 1952.
• The molecular defect responsible for XLA has been identified as a mutation in the BTK gene (Bruton's tyrosine kinase).
• BTK is a kinase involved in signal transduction pathways crucial for the maturation of B cells.

Aide-memoire

• Boys, Bruton, B cells, and BTK - an easy way to remember the key features of XLA, which primarily affects male children due to its X-linked inheritance.

Aetiology

• The BTK gene defect causes a failure in the maturation of B cells, leading to severely reduced circulating B cells and plasma cells.
• This results in the inability to produce sufficient antibodies (immunoglobulins), leaving patients vulnerable to infections.

Clinical Features

• Problems typically begin after 6 months of age when maternal Ig levels decrease.
• Primarily presents in boys with recurrent and severe bacterial infections.
• Patients often have small lymph nodes and absent tonsils due to the lack of mature B cells.
• Common infections include bacterial meningitis, joint infections, otitis media, and pneumonia.
• Pathogens include Mycoplasma, Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus.

Investigations

• Full Blood Count (FBC): Shows an absence of circulating B cells.
• Immunoglobulin levels are profoundly low, with decreased levels of IgG, IgM, and IgA.
• ↓ IgG ↓ IgM ↓ IgA with absent B cells.

Management

• The mainstay of treatment is immunoglobulin replacement therapy (Ig therapy), which successfully reduces the frequency and severity of infections.
• Avoid live vaccines, as these can pose a risk to immunocompromised patients.

Long-term Complications

• Patients may develop juvenile rheumatoid arthritis or aseptic polyarthritis.
• Other complications include dermatomyositis and an increased risk of colorectal neoplasms.